MODULATION OF CALCIUM CHANNELS BY METABOTROPIC GLUTAMATE RECEPTORS INCEREBELLAR GRANULE CELLS

We investigated the mechanisms by which metabotropic glutamate recepto rs (mGluRs) modulate specific Ca2+ channels in cerebellar granule cell s. A large fraction of the current in granule cells is carried by L- a nd Q-type Ca2+ channels (about 26% each), whereas N- and P-type contri bute proportionally less to the global current (9 and 15%, respectivel y). 1-Aminocyclopentane-dicarboxylate (t-ACPD), (2S,3S,4S)-alpha-(carb oxycyclopropyl)-glycine (L-CCGI) and (S)-4-carboxy-3-hydroxyphenylglyc ine [(S)-4C3HPG], but not L(+)-2-amino-4-phosphonobutyrate (L-AP4) red uced the Ca2+ current amplitude. The t-ACPD-induced inhibition was ful ly antagonized by(+)-methyl-4-carboxyphenylglycine [(+/-)-MCPG] and bl ocked by pertussis toxin (PTX). These results are consistent with inhi bitory response mediated by mGluR2/R3. The use of specific Ca2+ channe l blockers provided evidence that mGluR2/R3 inhibited both L- and N-ty pe Ca2+ currents. In PTX-treated cells, Glu or t-ACPD, but not L-CCGI or L-AP4, increased the Ca2+ current. Consistent with the activation o f mGluR1, the antagonists (+)-MCPG and (S)-4C3HPG prevented the facili tation of Ca2+ current produced by t-ACPD. The mGluR1-activated facili tation was completely blocked by nimodipine, indicating that L-type Ca 2+ currents were selectively potentiated.